Radiotherapy Research Today is a free monthly online journal that collates and summarizes the latest research about Radiotherapy, including details on cancer treatment, side effects.

213Bi (alpha-emitter)-antibody targeting of breast cancer metastases in the neu-N transgenic mouse model.

Song H, Shahverdi K, Huso DL, Esaias C, Fox J, Liedy A, Zhang Z, Reilly RT, Apostolidis C, Morgenstern A, Sgouros G

Divisions of Nuclear Medicine and Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Treatment failure in breast cancer is largely the failure to control metastatic dissemination. In this study, we investigated the efficacy of an antibody against the rat variant of HER-2/neu, labeled with the alpha-particle emitter (213)Bi to treat widespread metastases in a rat/neu transgenic mouse model of metastatic mammary carcinoma. The model manifests wide-spread dissemination of tumor cells leading to osteolytic bone lesions and liver metastases, common sites of clinical metastases. The maximum tolerated dose was 120 muCi of (213)Bi-7.16.4. The kinetics of marrow suppression and subsequent recovery were determined. Three days after left cardiac ventricular injection of 10(5) rat HER-2/neu--expressing syngeneic tumor cells, neu-N mice were treated with (a) 120 muCi (213)Bi-7.16.4, (b) 90 muCi (213)Bi-7.16.4, (c) 120 muCi (213)Bi-Rituximab (unreactive control), and (d) unlabeled 7.16.4. Treatment with 120 muCi (213)Bi-7.16.4 increased median survival time to 41 days compared with 28 days for the untreated controls (P < 0.0001); corresponding median survival times for groups b, c, and d were 36 (P < 0.001), 31 (P < 0.01), and 33 (P = 0.05) days, respectively. Median survival relative to controls was not significantly improved in mice injected with 10-fold less cells or with multiple courses of treatment. We concluded that alpha-emitter (213)Bi-labeled monoclonal antibody targeting the HER-2/neu antigen was effective in treating early-stage HER-2/neu--expressing micrometastases. Analysis of the results suggests that further gains in efficacy may require higher specific activity constructs or target antigens that are more highly expressed on tumor cells.

Published 16 May 2008 in Cancer Res, 68(10): 3873-80.
Full-text of this article is available online (may require subscription).

© 2004-2008 Radiotherapy Research Today. All Rights Reserved.